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Sinomenine Attenuates Traumatic Spinal Cord Injury by Suppressing Oxidative Stress and Inflammation via Nrf2 Pathway

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Abstract

Traumatic spinal cord injury (SCI) is a devastating condition with few efficacious drugs. Sinomenine, a bioactive alkaloid extracted from medicinal herb, has been used as a treatment of rheumatoid diseases. This present study explored the therapeutic effects of sinomenine on locomotor dysfunction and neuropathology in SCI. Our findings revealed that sinomenine mitigated neurological deficits and enhanced neuronal preservation, paralleled with a reduction of apoptosis. Also, sinomenine significantly reduced inflammatory cytokines and oxidative stress factors. We further examined erythroid-2-related factor 2 (Nrf2) nuclear translocation, which mainly controls the coordinated expression of important antioxidant and detoxification genes. An increase in Nrf2 translocation from cytoplasm to nucleus and Nrf2-mediated transactivation was observed after sinomenine administration. Knocking down Nrf2 by siRNA could counteract sinomenine-mediated anti-oxidant stress and anti-inflammation following H2O2-stimulated and LPS-stimulated PC12 cells. Together, our findings indicated that sinomenine has the potential to be an effective therapeutic agent for SCI by inhibiting inflammation and oxidative stress via Nrf2 activation.

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Acknowledgements

This work was supported by the Science and technology project of the National Natural Science Foundation of China (NO. 81401162), the Public Technology Research Program of Zhejiang Province (LGF18H060011) and Science and Technology Planning Program of Taizhou City (1702KY04).

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  1. Lilian Zhang and Weijiang Zhang contribute equally to this work.

Authors and Affiliations

  1. Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China

    Lilian Zhang, Weijiang Zhang & Naifeng Tian

  2. Zhejiang Provincial Key Laboratory of Orthopaedics, Wenzhou, 325000, Zhejiang, China

    Lilian Zhang, Weijiang Zhang & Naifeng Tian

  3. Department of Orthopaedics, Taizhou Hospital, Wenzhou Medical University, Linhai, 317000, Zhejiang, China

    Binbin Zheng

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  1. Lilian Zhang
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Correspondence to Binbin Zheng or Naifeng Tian.

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Zhang, L., Zhang, W., Zheng, B. et al. Sinomenine Attenuates Traumatic Spinal Cord Injury by Suppressing Oxidative Stress and Inflammation via Nrf2 Pathway. Neurochem Res 44, 763–775 (2019). https://doi.org/10.1007/s11064-018-02706-z

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